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Current Pharmaceutical Biotechnology - Online First
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Gossypetin Alleviates DSS-induced Colitis by Regulating COX2 and ROS–JNK Signaling
Available online: 26 November 2024More LessBackgroundInflammatory Bowel Disease (IBD) represents a chronic and recurrent inflammatory condition affecting the gastrointestinal tract, with a rising global incidence. Current treatment approaches include surgery and drugs. However, surgeries are invasive procedures, while drug treatments often present with various side effects. Gossypetin, a flavonoid found abundantly in plants such as hibiscus, exhibits anti-oxidant and anti-cancer properties. However, its potential impact on IBD remains unexplored.
ObjectiveThis study aimed to investigate the therapeutic potential of gossypetin on colitis.
MethodsWe employed the DSS-induced colitis model to evaluate the therapeutic potential of gossypetin on colitis. The efficacy of gossypetin was assessed within this model using the Disease Activity Index (DAI) score and histological analysis. Additionally, we utilized qRT-PCR to measure the levels of inflammatory cytokines and Superoxide Dismutase (SOD). Immunohistochemistry confirmed the expression of tight junction markers, COX-2, and phosphorylated JNK protein, normally associated with disease progression. Furthermore, Western blot analysis was conducted to examine the SOD levels and anti-apoptotic effects of gossypetin.
ResultsIn DSS-induced colitis mice, gossypetin treatment ameliorated weight loss and reduced colon length caused by DSS treatment. Additionally, gossypetin-treated groups exhibited DAI scores and reduced histological damage. Moreover, gossypetin treatment increased tight junction expression, decreased inflammatory responses, reduced ROS levels, attenuated JNK signaling, and decreased apoptosis.
ConclusionGossypetin shows therapeutic potential for mitigating the symptoms and progression of colitis by targeting ROS–JNK signaling involved in inflammation and tissue damage. This highlights the potential of natural compounds such as gossypetin for targeted therapies with reduced side effects and improved efficacy.
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Therapeutic Modulation of the Microbiome in Oncology: Current Trends and Future Directions
Authors: Istuti Saraswat and Anjana GoelAvailable online: 14 November 2024More LessCancer is a predominant cause of mortality worldwide, necessitating the development of innovative therapeutic techniques. The human microbiome, particularly the gut microbiota, has become a significant element in cancer research owing to its essential role in sustaining health and influencing disease progression. This review examines the microbiome's makeup and essential functions, including immunological modulation and metabolic regulation, which may be evaluated using sophisticated methodologies such as metagenomics and 16S rRNA sequencing. The microbiome influences cancer development by promoting inflammation, modulating the immune system, and producing carcinogenic compounds. Dysbiosis, or microbial imbalance, can undermine the epithelial barrier and facilitate cancer. The microbiome influences chemotherapy and radiation results by modifying drug metabolism, either enhancing or reducing therapeutic efficacy and contributing to side effects and toxicity. Comprehending these intricate relationships emphasises the microbiome's significance in oncology and accentuates the possibility for microbiome-targeted therapeutics. Contemporary therapeutic approaches encompass the utilisation of probiotics and dietary components to regulate the microbiome, enhance treatment efficacy, and minimise unwanted effects. Advancements in research indicate that personalised microbiome-based interventions, have the potential to transform cancer therapy, by providing more effective and customised treatment alternatives. This study aims to provide a comprehensive analysis of the microbiome's influence on the onset and treatment of cancer, while emphasising current trends and future possibilities for therapeutic intervention.
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Virus-like Particles-Based Vaccine to Combat Neurodegenerative Diseases
Available online: 29 October 2024More LessNeurodegenerative diseases are regarded as gradual, incurable conditions with an insidious onset. Alzheimer’s disease (AD) and Parkinson’s disease (PD) are two of the most prevalent neurodegenerative diseases reported globally. Developing effective treatment strategies for neurodegenerative diseases has remained a primary objective and a huge challenge for researchers. The therapeutic medications that are now approved for the treatment of neurodegenerative diseases merely treat the symptoms; the underlying pathology is not addressed. Therefore, the emergence of novel disease-modifying therapeutic modalities such as immunotherapy has opened a new path in developing effective treatments for neurogenerative diseases. Compared to other types of subunit active vaccines, virus-like particles (VLPs) are considerably more immunogenic as they present dense and repetitive viral antigen epitopes on their surface, which can trigger both humoral and cell-mediated immune responses. They are also a much safer option than the traditional inactivated and live-attenuated vaccines since they are devoid of viral genomes and are, therefore, non-pathogenic and non-infectious. Researchers have turned their attention to VLPs as an active immunotherapy candidate for AD due to the lessons learned from the AN1792 trial. Studies have shown that they effectively induce anti-Aβ, anti-tau, and anti-α-Synuclein antibodies while avoiding T-cell-related immune reactions in animal models of AD and PD. This review compiles the findings of preclinical animal model studies and clinical investigations on VLP-based vaccines for neurogenerative diseases thus far. The technical limitations and potential difficulties associated with the future application of VLP-based vaccines in patients with neurodegenerative diseases have also been covered.
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Tryptophan Stability and Palatability in the Food Formulation: A Review
Available online: 29 October 2024More LessTryptophan, an essential amino acid, plays a vital role in the synthesis of critical compounds like serotonin, melatonin, and niacin, which impact mood, sleep, and metabolic processes. It holds promise for improving the well-being of individuals with mood issues or sleep disorders through dietary enrichment. However, incorporating tryptophan into food products presents challenges related to stability, bitterness, and susceptibility to oxidative degradation. These issues can reduce consumer acceptability and effectiveness and may lead to the formation of harmful byproducts. This review comprehensively examines innovative strategies for enriching food products with tryptophan. Crucial approaches include using nano-emulsion systems to encapsulate tryptophan, thereby protecting it from environmental factors and enhancing its bioavailability, adding antioxidants to prevent degradation, and utilizing functional derivatives as alternatives to pure tryptophan. These strategies aim to improve the stability of tryptophan, reduce bitterness, and enhance consumer acceptability. This review provides valuable insights into practical methods for incorporating tryptophan into food formulations, with the goal of optimizing its health benefits and ensuring a positive consumer experience.
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Mechanisms of Bioactive Lipids to Modulate Master Regulators of Lipid Homeostasis and Inflammation in Metabolic Syndrome
Available online: 25 October 2024More LessMetabolic Syndrome (MetS) refers to the co-occurrence of a constellation of metabolic diseases in the same individual, such as abdominal/visceral obesity, insulin resistance or diabetes, alterations in the lipid profile (dyslipidemias), and/or hypertension, which promotes the development of other cardiometabolic and hepatic diseases. Dyslipidemia and metabolic dysfunction-associated steatotic liver disease (MASLD), previously termed nonalcoholic fatty liver disease (NAFLD), are common MetS pathologies closely related to lipid metabolism. Alterations in the metabolism of proteins, carbohydrates, and lipids, caused by an excessive intake of nutrients and abnormal accumulation of body fat, which promotes chronic low-grade inflammation, are pivotal aspects of MetS development. To avoid damage caused by lipid overaccumulation, the transcription factors responsible for regulating lipid homeostasis and inflammation (named in this work master regulators) must modify their regular activity however, the high adiposity established for long periods causes the appearance of insulin resistance (the MetS triggering factor most widely accepted in the literature). Fortunately, scientific evidence suggests that the abnormal activity of these regulators can be conveniently modulated by distinct species of bioactive lipids, among which unsaturated fatty acids stand out, offering new alternatives for treating MetS. Therefore, this work aims to provide a general overview of scientific evidence that supports the mechanisms of action and the effective modulation by bioactive lipids of some master lipid-metabolism-and-inflammation regulators in diverse aspects of MetS
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Discovery of New Natural Phytocompounds: The Modern Tools to Fight Against Traditional Bacterial Pathogens
Available online: 21 October 2024More LessOngoing competition between disease-causing bacteria and human hosts has resulted in the discovery of a wide array of antibacterials. The advent of antibacterials ushered in a promising period in the realm of microbiology, but its brilliance was short-lived and soon diminished. The excessive and incorrect use of antibacterials results in limited selection pressure on the targeted microorganisms, which in turn promotes the evolution of microbes instead of killing them. Consequently, antibacterial resistance has developed and given rise to strains that are resistant to many drugs, leading to a significant increase in mortality rates. The current review delves into the potential of novel natural phytocompounds as innovative solutions to combat these potential bacterial threats. The review begins by showcasing the modus operandi of conventional antibacterial drugs followed by addressing the mechanisms of resistance to antibacterial agents, which have significantly lowered the efficacy of conventional treatments. In contrast, the review explores the mechanism of antibacterial activity of plant-derived phytochemicals, unraveling the various ways in which natural compounds interact with bacterial targets. Furthermore, the review examines the synergism between plant phytochemicals and conventional antibiotics, showcasing the efficacy of this combinatorial approach in overcoming resistance. The review concludes by summarizing the current research and offering valuable insights into challenges in the use of plant phytochemicals as antibacterial therapeutics. This comprehensive overview reinforces the promise of incorporating modern scientific tools with traditional phytotherapy to develop effective strategies against resistant bacterial pathogens.
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Unwinding the Threads of Mesoporous Silica Nanoparticles as Cutting-Edge for the Management of Inflammation: An Updated Review
Authors: Priya Dhiman, Sukhbir Singh, Sandeep Arora, Neelam Sharma, Ritu Gulia and Ladli KishoreAvailable online: 11 October 2024More LessBackgroundInflammation serves as a protective response to combat cellular and tissue damage. There is currently a wide array of synthetic and traditional therapies available for the treatment of inflammatory diseases. However, it is necessary to create a drug delivery system based on nanotechnology that can improve the solubility, permeability, and bioavailability of current treatments. Mesoporous silica nanoparticles (MSNPs) are inorganic materials known for their organised porous interiors, high pore volumes, substantial surface area, exceptional selectivity, permeability, low refractive index, and customisable pore sizes.
ObjectiveThis review offers concise insights into the progression of the pathophysiology of inflammation, as well as the inducers, mediators, and effectors that are involved in the inflammatory pathway. This study focuses on the growing significance of MSNPs in the treatment of neuroinflammation, inflammatory bowel disease, arthritic inflammation, lung inflammation, and wound healing applications. This review also presents the latest information on the crucial role of MSNPs in delivering herbal medicines for the treatment of inflammation.
MethodsA comprehensive literature search was conducted for this aim, utilising the Google Scholar, PubMed, and ScienceDirect databases. A systematic review was undertaken utilising scholarly articles published in peer-reviewed journals from 2000 to 2024.
ResultsThe inflammatory mediators involved in the pathophysiology of inflammation include platelet-activating factor, lipoxygenase, cyclooxygenase, Interferon-α, interleukin-6, interleukin-1β, matrix metalloproteinases, inducible nitric oxide synthase, nuclear factor-κB, prostaglandins, nitric oxide, and phospholipase A2. MSNPs have the potential to be used in the treatment of neuroinflammation, inflammatory bowel disease, arthritic inflammation, lung inflammation, and wound healing. The investigation of the MSNPs of plant-based compounds such as berberine, tetrahydrocannabinol, curcumin, and resveratrol has shown successful results in recent years for the purpose of managing inflammation.
ConclusionThis review demonstrates that MSNPs have a strong potential to play a positive role in delivering synthetic and plant-based therapies for the treatment of inflammatory illnesses.
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Role of Medicinal Plants in the Management of Multiple Sclerosis
Authors: Aaryan Gupta, Arpita Roy, Amit Roy, Vaseem Raja, Kuldeep Sharma and Rajan VermaAvailable online: 10 October 2024More LessThere is a rapid spread of Multiple Sclerosis disorder across the globe, around 2.8 million cases of Multiple Sclerosis in the world. Multiple Sclerosis (MS) is a chronic autoimmune disease of the central nervous system characterized by demyelination, neuroinflammation, and a wide spectrum of clinical manifestations. Many drugs have been tested on MS patients but there is no effective treatment for MS till now. So to inhibit the symptoms caused by MS we performed a study in which we identified various naturally occurring materials with neuroprotective effects on the body that can treat Multiple Sclerosis. The therapeutic strategies portion of the paper reviews the array of disease-modifying therapies currently available for MS management. This paper evaluated their mechanisms of action, efficacy, and safety profiles. It also addressed emerging treatment paradigms by using different naturally occurring materials, including personalized medicine approaches and novel therapies in development. This paper provides a comprehensive overview of the current state of knowledge regarding MS, focusing on its pathogenesis, diagnostic approaches, and therapeutic strategies.
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Jiangu Recipe Suppresses ER Stress-Induced Apoptosis and Inhibits Extracellular Matrix Degradation in Chondrocytes through Upregulating SIRT1 Expression
Authors: Jie Qiao, Chang Cheng, Gongxu Yang, Chuanqi Zhong, Jun Jin and Bin WuAvailable online: 09 October 2024More LessObjectiveThis study aimed to explore the effects of Jiangu Recipe (JGR) on chondrocyte responses under tert-Butyl hydroperoxide (TBHP)-induced oxidative stress, specifically focusing on apoptosis and extracellular matrix (ECM) degradation.
MethodsChondrocytes were treated with varying JGR concentrations, and cell viability was assessed. The impact of JGR on TBHP-induced apoptosis and protein expression levels of apoptosis-related molecules (Bcl-2, Bax, and cleaved caspase-3) and ECM components (Collagen II, Aggrecan, MMP-13) was evaluated.
ResultsJGR exhibited protective effects against oxidative stress in chondrocytes. Moreover, it maintained cell viability under tert-butyl hydroperoxide (TBHP) induction, suppressing apoptosis (Bax, cleaved caspase-3) and enhancing anti-apoptotic Bcl-2. JGR also attenuated extracellular matrix (ECM) degradation, promoting Collagen II and Aggrecan while reducing MMP-13 expression. Investigating endoplasmic reticulum (ER) stress, it was found that JGR downregulated TBHP-induced GRP78, CHOP, ATF4, p-PERK, and p-eIF2α, thus indicating ER stress modulation. SIRT1 played a key role, as JGR upregulated SIRT1, mitigating TBHP-induced downregulation. SIRT1 knockdown reversed JGR's protective effects, highlighting its crucial role in JGR-mediated responses.
ConclusionOur findings suggest that JGR mitigated TBHP-induced chondrocyte apoptosis and ECM degradation, highlighting its potential therapeutic application in osteoarthritis. Mechanistically, our study highlights that SIRT1 plays a crucial role in mediating the protective effects of JGR against ER stress-induced chondrocyte apoptosis and ECM degradation, providing a foundation for further clinical exploration in managing osteoarthritic conditions.
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Bridging the GAP: Probiotic Douches Redefining the Feminine Hygiene
Authors: Akash Kumar, Sadique Hussain, Nitya Srivastava, Gurvinder Singh, Monica Gulati and Rajesh KumarAvailable online: 09 October 2024More LessVaginal douching is a centuries-old practice which is still in use, especially among adolescents. “Probiotic douches” are the vaginal douches that are formulated with probiotics and are intended to restore or maintain the vaginal microbiome balance. Probiotic douches are a new type of feminine hygiene product that claims to promote a balanced vaginal microbiome and improve overall well-being. However, the evidence supporting the use of probiotics for vaginal health is limited because of the variability in probiotic strains and dosages studied, and the lack of more comprehensive, long-term clinical trials. Most of the existing scientific literature on probiotics focuses on oral probiotic supplements and vaginal probiotic suppositories. Some potential benefits of probiotic douches include restoring a balanced vaginal microbiota, preventing, or managing infections, supporting local immune function, reducing odor and discharge, and enhancing overall vaginal comfort. However, it is important to note that these benefits have not been definitively proven and remain a subject of ongoing research. There are also potential risks associated with their use including disruption of the natural vaginal ecosystem by introducing foreign substances, risk of infection, and stability issues with the formulation that may lead to negative consequences. This review attempts to comprehend the critical need for robust scientific research to guide the safe and effective incorporation of probiotic douches into modern feminine hygiene practices, revolutionizing women's health, and well-being.
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Integrated Transcriptomics and Metabolomics Studies Reveal Steroid Biosynthesis Pathway and BCL2 Inhibitory Diazo-Progesterone of Drimia indica for Conservation and Sustainable Utilization
Authors: Vivek Shit, Mahesh Kumar Dhakar and Manoj KumarAvailable online: 09 October 2024More LessBackgroundThis study is the first report on the sequence of the transcriptome of Drimia indica, a non-model plant with medicinal properties found in a forest tribal belt, using the Illumina NovaSeq platform. The primary objectives of this study were to elucidate the gene expression profiles in different tissues, identify key regulatory genes and pathways involved in secondary metabolite biosynthesis, and explore the plant's potential pharmacological properties.
MethodsThe study generated 670087 unigenes from both leaves and roots and identified putative homologs of annotated sequences against UniProt/Swiss-Prot and KEGG databases. The functional annotation of the identified unigenes revealed the secondary metabolite biosynthetic process as the most prominent pathway, with gene enrichment analysis predominantly accounting for secondary metabolite pathways, such as terpenoid, steroid, flavonoid, alkaloid, selenocompound, and cortisol synthesis. The study also identified regulatory genes NAC, Bhlh, WRKY, and C2H2 on the transcriptome dataset.
ResultsThe functionally annotated unigenes suggested phytocompounds in Drimia indica to have multi-potent properties, such as anti-cancer, anti-inflammatory, and anti-diabetic activities, which has been further validated by GC-MS-based metabolite profiling. Notably, we have identified two novel molecules, di-azo progesterone and 4H-pyran-4-one 2,3-dihydro-3,5-dihydroxy-6-methyl, with potential BCL2 inhibitory anticancer properties, supported by stable binding interactions observed in molecular docking and dynamics simulations. Additionally, an abundance of mono-nucleotide SSR markers has been identified, useful for genetic diversity studies.
ConclusionThis study provides a foundational understanding of the molecular mechanisms in Drimia indica, highlighting its potential as a source for novel therapeutic agents and contributing valuable insights for future pharmacological and agricultural applications. However, further in vivo studies are warranted to confirm these findings and validate their pharmacological efficacy and therapeutic potential. The SSR markers identified also offer valuable tools for molecular genetics, plant breeding, and sustainable drug development.
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Advances in Colon-Targeted Drug Delivery Systems: Innovative Strategies for Treating Colonic Disorders and Prospects for the Future
Authors: Jyoti Singh, Ashutosh Solanki, Gaurav Singh Sikarwar and Niraj Kumar SinghAvailable online: 09 October 2024More LessColon-specific targeting delivery systems have drawn a great deal of attention because they represent potential vehicles for treating colonic disorders like diverticulitis, colitis, salmonellosis, Crohn’s disease, etc. with less systemic adverse effects as well as for the better oral delivery of many therapeutics that are prone to enzymatic and acidic deterioration in the upper GI tract. Smart polymeric delivery systems in particular have been investigated as "intelligent" delivery systems capable of releasing entrapped pharmaceuticals at the proper time & site of action in response to certain physiological stimuli. The creation of novel polymers & crosslinkers with improved biodegradability and biocompatibility would expand and enhance applications now in use. The development of polymeric systems could result in more precise and programmable drug delivery/therapies. In addition, newer advancements have led to the development of numerous ground-breaking techniques for directing a medication molecule to the colon. This review highlighted formulation techniques pH-dependent, time-dependent, enzyme sensitive, magnetically dependent, ligand-receptor mediated, and microflora-activated systems. Moreover, several methods have been put forth that make use of the innovative idea of such delivery systems, and mechanisms in which the release of drugs is regulated by pH and time as well as pH and the colon's bacteria.
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Dihydroartemisinin Modulates Prostate Cancer Progression by Regulating Multiple Genes via the Transcription Factor NR2F2
Authors: Yong Shao, Yunhui Chan, Chuan Zhang, Rong Zhao and Yuxin ZuAvailable online: 03 October 2024More LessObjectiveThis study aimed to investigate the effect of dihydroartemisinin (DHA) on DU145 cells and the role of NR2F2 (COUP-TFII) and its potential target genes in this process.
MethodsGSE122625 was used to identify differentially expressed genes (DEGs) between the DHA-treated and control groups. Protein-protein interaction (PPI) network analysis was performed to identify hub genes, and the ChEA3 database was used to identify potential transcription factors. qRT-PCR and Western blot were used to validate the expression of genes of interest and functional assays were performed to evaluate the effect of DHA on DU145 and PC-3 cells. To solidify the regulatory relationship of NR2F2 with EFNB2, EBF1, ETS1, and VEGFA, a Chromatin Immunoprecipitation (ChIP) experiment was performed.
ResultsWe identified 85 DEGs in DU145 cells treated with DHA, and PPI network analysis identified NR2F2 as a hub gene and potential transcription factor. The regulatory network of NR2F2 and its potential target genes (EFNB2, EBF1, ETS1, and VEGFA) was constructed, and the expression of these genes was upregulated in DHA-treated cells compared to control cells. Functional assays showed that DHA treatment inhibited epithelial-mesenchymal transition, reduced inflammation, and promoted apoptosis in DU145 and PC-3 cells. Furthermore, NR2F2 knockdown receded the DHA-induced upregulation of target genes and functional changes of DU145 and PC-3 cells. The outcomes of ChIP unequivocally pointed to a positive regulatory role of NR2F2 in these gene expressions.
ConclusionOur study suggests that DHA treatment affects the functions of DU145 and PC-3 cells by regulating the expression of NR2F2 and its potential target genes, and NR2F2 may serve as a potential therapeutic target for prostate cancer.
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The Gut Health Revolution: Herbs and Dietary Phytochemicals in Balancing Gut Microbiota for Optimal Human Health
Available online: 27 September 2024More LessThe gut microbiota is a varied population of microorganisms that live in the human gastrointestinal system. Emerging research emphasizes the importance of this microbial ecology in general health and its influence on a variety of disorders. The review explores the synergy between herbal treatment and traditional medicine, emphasizing their cultural significance and therapeutic benefits. It delves into the intricate relationship between herbal remedies, traditional healing practices, and their sustained usage over centuries. The review highlights the pivotal role of the gut microbiota in herbal medicine, elucidating how treatments influence the gastrointestinal microorganisms, impacting overall health. Dietary phytochemicals are underscored for their significance in herbal medicine and nutritional well-being, along with the interdependence of plant extracts and botanicals. The investigation explores the molecular connections between phytoconstituents and gut microbiota, aiming to deepen the understanding of herbal medicine's tailored approach to specific health challenges. The summary concludes by emphasizing herbal treatments' unique ability to regulate gut flora, contributing to overall gastrointestinal well-being. In closing, the review provides a concise overview, serving as a valuable resource for integrative medicine research, with recommendations for future exploration of herbal medicine's potential in healthcare.
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Biomarkers and Novel Therapies of Diabetic Neuropathy: An Updated Review
Available online: 27 September 2024More LessDiabetic neuropathy is a persistent consequence of the biochemical condition known as diabetes mellitus. As of now, the identification and management of diabetic neuropathy continue to be problematic due to problems related to the safety and efficacy of existing therapies. This study examines biomarkers, molecular and cellular events associated with the advancement of diabetic neuropathy, as well as the existing pharmacological and non-pharmacological treatments employed. Furthermore, a holistic and mechanism-centric drug repurposing approach, antioxidant therapy, Gene and Cell therapies, Capsaicin and other spinal cord stimulators and lifestyle interventions are pursued for the identification, treatment and management of diabetic neuropathy. An extensive literature survey was done on databases like PubMed, Elsevier, Science Direct and Springer using the keywords “Diabetic Neuropathy”, “Biomarkers”, “Cellular and Molecular Mechanisms”, and “Novel Therapeutic Targets”.Thus, we may conclude that non-pharmacological therapies along with palliative treatment, may prove to be crucial in halting the onset of neuropathic symptoms and in lessening those symptoms once they have occurred.
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A Comprehensive Pan-Cancer Analysis Identified that TRIB3 was Associated with Immune Cell Infiltration and Poor Prognosis
Authors: Ke-Xun Yu, Wei-Jie Yuan, Jing-Li, Hui-Zhen Wang and Yong-Xiang LiAvailable online: 12 September 2024More LessBackgroundPrevious studies have demonstrated that TRIB3 plays a carcinogenic role in tumor progression. However, the exploration of TRIB3 at the pan-cancer level has not been reported.
AimsThis study aimed to conduct a comprehensive pan-cancer analysis of TRIB3.
ObjectiveWe explored the expression pattern and functional mechanism of TRIB3 on the basis of multiple databases.
MethodWe first explored the expression level of TRIB3 in the TCGA database. Then, the receiver operation characteristic curve (ROC), Kaplan-Meier plotter, and Cox regression were used to estimate the diagnostic and prognostic value of TRIB3, respectively. We also explored the relationship between TRIB3 and the infiltration of tumor immune cells, as well as the expression of immune checkpoint molecules. Gene enrichment and protein interaction network analysis were carried out to identify possible carcinogenic molecular mechanisms and functional pathways. Finally, we compared the non-promoter region methylation of TRIB3 in normal and tumor tissues and explored potential systems with unique functions in TRIB3-mediated tumorigenesis.
ResultThe expression level of TRIB3 was elevated in multiple tumor types, and the high expression of TRIB3 was associated with poor prognosis. TRIB3 had a higher frequency of genetic changes in several tumors and showed varying trends in TRIB3 methylation levels. Additionally, high expression of TRIB3 was also associated with infiltration of cancer-related fibroblasts and different types of immune cells and was positively correlated with the expression of immune checkpoint molecules. Furthermore, gene enrichment analysis suggested that TRIB3 may play a role in the malignant progression of cancer by participating in protein post-translational modifications and activating transcription initiation factors.
ConclusionOur pan-cancer analysis provided the potential carcinogenic role of TRIB3 in tumors and verified a promising target for clinical immune treatment.
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cRGD-platelet@MnO/MSN@PPARα/LXRα Nanoparticles Improve Atherosclerosis in Rats by Inhibiting Inflammation and Reducing Blood Lipid
Authors: Zheng Lv, Yupeng Zhang, Mengke Lu, Ziyi Wang, Xiaoyue Nong, Guoliang Wen and Wei ZhangAvailable online: 02 September 2024More LessObjectiveAtherosclerosis (AS) is an inflammatory disease of arterial intima driven by lipids. Liver X receptor alpha (LXRα) and peroxisome proliferator-activated receptor alpha (PPARα) agonists are limited in the treatment of AS due to their off-target effects and serious side effects. Therefore, this study was designed to construct a novel nanoparticle (NP) and evaluate its mechanism of action on inflammation inhibition and lipid reduction in AS.
MethodsWe synthesized cRGD-platelet@MnO/MSN@PPARα/LXRα NPs (cRGD-platelet-NPs) and confirmed their size, safety, and targeting ability through various tests, including dynamic light scattering and immunofluorescence. In vivo and in vitro experiments assessed cell proliferation, apoptosis, inflammation, and plaque formation. Finally, the NF-κB signaling pathway expression in rat aorta was determined using a western blot.
ResultsThe synthesis of cRGD-platelet-NPs was successful; the particle size was approximately 150 nm, and the PDI was below 0.3. They could be successfully absorbed by cells, exhibiting high safety in vivo and in vitro. The cRGD-platelet-NPs successfully reduced plaque formation, improved lipid profiles by lowering LDL-cholesterol, total cholesterol, and triglycerides, and raised HDL-cholesterol levels. Additionally, they decreased inflammatory markers in the serum and aortic tissue, suggesting reduced inflammation. Immunohistochemistry and western blot analyses indicated that these NPs could not only promote M2 macrophage polarization but also suppress the NF-κB signaling pathway.
ConclusionThe newly developed cRGD-platelet-NPs with high safety are a promising approach to AS treatment, which can regulate ABCA1, reduce the formation of AS plaques, and enhance cholesterol efflux. The mechanism may involve the suppression of the NF-κB signaling pathway.
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Recent Advances in Immunotherapy and Targeted Therapy of Triple Negative Breast Cancer
Authors: Harshada Shewale and Abhishek KanugoAvailable online: 31 July 2024More LessThe truancy of representation of the estrogen, progesterone, and human epidermal growth factor receptors occurs during TNBC. TNBC is recognized for the upper reappearance and has a poorer diagnosis compared with rest breast cancer (BC) types. Presently, as such, no targeted therapy is approved for TNBC and treatment options are subjected to chemotherapy and surgery, which have high mortality rates. Hence, the current article focuses on the scenario of TNBC vital pathways and discusses the latest advances in TNBC treatment, including immune checkpoint inhibitors (ICIs), PARP suppressors, and cancer vaccines. Immunotherapy and ICIs, like PD 1 and PD L1 suppressors, displayed potential in clinical trials (CTs). These suppressors obstruct the mechanisms which allow tumor cells to evade the system thereby boosting the body’s defense against TNBC. Immunotherapy, either alone or combined with chemotherapy has demonstrated patient outcomes such as increased survival rates and reduced treatment-related side effects. Additionally, targeted therapy approaches include BRCA/2 mutation poly ribose polymerase inhibitors, Vascular Endothelial Growth Factor Receptor (VEGFR) inhibitors, Epidermal growth factor receptor inhibitors, Fibroblast growth factor inhibitors, Androgen Receptor inhibitors, PIK3/AKT/mTOR pathway inhibitors, Cyclin-dependent kinase (CDK) inhibitors, Notch signaling pathway inhibitors, Signal transducer and activator of transcription 3 (STAT3) signaling pathway inhibitors, Chimeric antigen receptor T (CAR-T) cell therapy, Transforming growth factor (TGF) -β inhibitors, Epigenetic modifications (EPM), Aurora Kinase inhibitors and antibody-drug conjugates. We also highlight ongoing clinical trials and potential future directions for TNBC therapy. Despite the challenges in treating TNBC, recent developments in understanding the molecular and immune characteristics of TNBC have opened up new opportunities for targeted therapies, which hold promise for improving outcomes in this aggressive disease.
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